This is a resubmission of a NIDA K02 Independent Investigator Award. The application proposes to provide the candidate, Tony P. George, M.D., with salary support over the next five years (2004-2009). Dr. George is currently an Assistant Professor in his sixth year on the psychiatry faculty at Yale University School of Medicine. Since joining the Yale faculty in 1998, Dr. George has developed a unique research program with a focus on understanding the effects of nicotine and tobacco use on cognitive and clinical function in patients with major psychiatric disorders, including schizophrenia. He has established an early record of significant publications, national recognition, and independent funding support in the area of nicotine and mental illness, including two NARSAD Young Investigator Awards, pilot studies in the Yale-VA MIRECC and the NIDA-funded Yale Transdisciplinary Tobacco Use Research Center, a Donaghue Medical Research Foundation grant, and two R01 grants from NIDA. The R01 grants have defined his translational focus on smoking and mental illness, and include a human laboratory study of smoking and cognitive function in schizophrenia (DA-14039, 20% effort with salary), and the development of a pharmacological treatment optimizing strategy for smoking cessation in schizophrenic patients using nicotine patch, bupropion and atypical antipsychotic drugs (DA-13672; 20% effort with salary). Accordingly, the receipt of a K02 award would allow him to: 1) continue to develop his independent research program at Yale and relieve the commitment of R01 funds from these projects to support his salary, and; 2) acquire knowledge and expertise in novel techniques from senior colleagues at Yale and elsewhere that are unfamiliar to him, including assessment of novel neuropsychological and psychophysiological endophenotypes, human molecular genetic and biochemical pharmacology techniques, and advanced biostatistical methods for smoking cessation clinical trials. To achieve these goals, he will organize a formal training program consisting of didactic instruction, guidance from senior colleagues and brief training experiences in the laboratories of collaborators working in these areas of interest. Ultimately, this K02 would support two new and integrated projects that will correlate neurocognitive, genetic and biochemical assessments with smoking cessation treatment response in schizophrenic patients.